Neuroprotective Effects of Acetylcholinesterase Inhibitory Peptides from Anchovy (Coilia mystus) against Glutamate-Induced Toxicity in PC12 Cells.

Abstract

Ameliorations of cholinergic system dysfunction and oxidative stress in neurodegenerative diseases were main approaches to improve memory disorder. Our previous investigation showed that anchovy protein hydrolysate (APH) could attenuate scopolamine-induced memory deficits in mice by regulating acetylcholinesterase (AChE) activity. Therefore, peptides with AChE inhibitory activity in APH were explored and identified in this study, and their possible neuroprotective mechanisms on glutamate induced apoptosis in PC12 were also elucidated. Two peptides with strong AChE inhibitory capacity were identified as Pro-Ala-Tyr-Cys-Ser (PAYCS) and Cys-Val-Gly-Ser-Tyr (CVGSY) by ultraperformance liquid chromatography coupled with tandem mass spectrometry. The AChE inhibitory was 23.68 ± 0.97% and 6.08 ± 0.41%, respectively. Treatment with PAYCS and CVGSY could significantly (p < 0.05) increase cells viability, reduce lactate dehydrogenase release, reactive oxygen species (ROS) production, malondialdehyde content, and the ratio of Bax/Bcl-2 of glutamate-induced apoptosis PC12 cells (82.78 ± 6.58 and 109.94 ± 7.16% of control, respectively) as well as increase superoxide dismutase and GSH-px activities. In addition, both the peptides could inhibit Ca2+ influx but have no effects on mitochondrial membrane potential. Results indicated that AChE inhibitory peptides (PAYCS and CVGSY) possibly protected the PC12 cells against glutamate-induced apoptosis via inhibiting ROS production and Ca2+ influx. PAYCS and CVGSY might be considered as nutraceuticals for alleviating memory deficits.

• Authors: Tiantian Zhao, Guowan Su, Shuguang Wang, Qi Zhang, Jianan Zhang, Lin Zheng, Baoguo Sun, Mouming Zhao
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 65 Issue 51 Pg. 11192-11201 (Dec 27 2017) ISSN: 1520-5118 [Electronic] United States
• PMID: 29190426 (Publication Type: Journal Article)

Chemical References

• Cholinesterase Inhibitors
• Fish Proteins
• Neuroprotective Agents
• Peptides
• Reactive Oxygen Species
• Glutamic Acid
• Malondialdehyde
• Glutathione Peroxidase
• Superoxide Dismutase
• Acetylcholinesterase

Topics

• Acetylcholinesterase (chemistry)
• Animals
• Apoptosis (drug effects)
• Cell Survival (drug effects)
• Cholinesterase Inhibitors (chemistry, pharmacology)
• Fish Proteins (chemistry, pharmacology)
• Fishes
• Glutamic Acid (toxicity)
• Glutathione Peroxidase (metabolism)
• Humans
• Malondialdehyde (metabolism)
• Memory Disorders (drug therapy, enzymology, metabolism, physiopathology)
• Neurons (cytology, drug effects, enzymology, metabolism)
• Neuroprotective Agents (chemistry, pharmacology)
• Oxidative Stress (drug effects)
• PC12 Cells
• Peptides (chemistry, pharmacology)
• Rats
• Reactive Oxygen Species (metabolism)
• Superoxide Dismutase (metabolism)